Severe
hypoglycemia constitutes a medical emergency, involving
seizures,
coma and death. We hypothesized that
seizures, during limited substrate availability, aggravate
hypoglycemia-induced brain damage. Using immature isolated, intact hippocampi and frontal neocortical blocks subjected to low
glucose perfusion, we characterized
hypoglycemic (neuroglycopenic)
seizures in vitro during transient
hypoglycemia and their effects on synaptic transmission and
glycogen content. Hippocampal
hypoglycemic seizures were always followed by an irreversible reduction (>60% loss) in synaptic transmission and were occasionally accompanied by spreading depression-like events.
Hypoglycemic seizures occurred more frequently with decreasing "
hypoglycemic" extracellular
glucose concentrations. In contrast, no
hypoglycemic seizures were generated in the neocortex during transient
hypoglycemia, and the reduction of synaptic transmission was reversible (<60% loss).
Hypoglycemic seizures in the hippocampus were abolished by
NMDA and non-
NMDA antagonists. The
anticonvulsant,
midazolam, but neither
phenytoin nor
valproate, also abolished
hypoglycemic seizures. Non-glycolytic, oxidative substrates attenuated, but did not abolish,
hypoglycemic seizure activity and were unable to support synaptic transmission, even in the presence of the
adenosine (A1) antagonist,
DPCPX. Complete prevention of
hypoglycemic seizures always led to the maintenance of synaptic transmission. A quantitative
glycogen assay demonstrated that
hypoglycemic seizures, in vitro, during
hypoglycemia deplete hippocampal
glycogen. These data suggest that suppressing
seizures during
hypoglycemia may decrease subsequent neuronal damage and dysfunction.